Phosphatidylethanolamines ("PEs") are naturally occurring phospholipids typically having two acyl chains, as well as a phosphorylethanolamine group, attached to the lipid's glycerol backbone. N-acylated phosphorylethanolamines ("NAPEs") are PEs to which an additional, third acyl chain has been attached, by way of the amino moiety of the lipids' phosphorylethanolamine group. Some NAPEs are also found in biological membranes, in small amounts.
Most PEs ordinarily do not organize into bilayers at neutral pH, instead forming hexagonal (H.sub.II)-phase structures in aqueous environments. Hexagonal-phase formation is a property that may be associated with enhanced liposome fusogenicity when these lipids are incorporated into liposomal bilayers under appropriate conditions (Verkleij, 1984; Cullis & de Kruijff, 1979; Ellens et al., 1989). NAPEs, by contrast, spontaneously form bilayers in aqueous dispersions, in the absence of added divalent cations (Newman et al., 1986; Akoka et al., 1988; Lafrance et al., 1990; Domingo et al., 1994).
None of the above documents describes a study of NAPEs with regard to their ability to be either fusogenic or bilayer-destabilizing at the desired delivery site, yet still be able to form liposomes that can stably encapsulate material. None of the previous studies describe the use to which NAPEs can be put to for the controlled delivery of liposomal drugs, and none describe tailoring NAPEs so as to optimize such delivery, especially in vivo. Moreover, none have either synthesized or studied the NAPE N-dodecanoyl dioleoyl phosphatidylethanolamine.